..Cellular responses to DNA damage are coordinated primarily by two distinct kinase signaling cascades, the ATM-Chk2 and ATR-Chk1 pathways, which are activated by DNA double-strand breaks (DSBs) and single-stranded DNA ..

..The rapid activation of p53 by ionizing radiation and radiomimetic agents is largely dependent on the ATM kinase. p53 is phosphorylated by ATM shortly after DNA damage, resulting in enhanced stability and activity of p53...

..Expression of Vpr, in particular, leads to cell cycle arrest in G(2), followed by apoptosis. Here we summarize our current understanding of Vpr biology with a focus on Vpr-induced G(2) arrest and apoptosis...

The cellular response to DNA double-strand breaks (DSBs) is mobilized by the protein kinase ATM, which phosphorylates key players in the DNA damage response (DDR) network. A major question is how ATM controls DSB repair...

..we demonstrated that, in Env-elicited syncytia, PML was required for activating phosphorylation of ataxia telangiectasia mutated (ATM), which colocalized with PML in nuclear bodies, in a molecular complex that also involved ..

..Although DNA-PKcs autophosphorylates itself at Ser-2056 after IR, we have reported here that ATM mediates DNA-PKcs phosphorylation at Thr-2609 as well as at the adjacent (S/T)Q motifs within the Thr-2609 cluster...

Hailiang HuDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, USAProc Natl Acad Sci U S A 107:1506-11. 2010

Ataxia-telangiectasia mutated (ATM) is a high molecular weight protein serine/threonine kinase that plays a central role in the maintenance of genomic integrity by activating cell cycle checkpoints and promoting repair of DNA double-..

Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1

..a mediator of DNA DSB signaling, but now it has been shown to function upstream of ataxia-telangiectasia mutated (ATM), in one of at least two parallel pathways leading to ATM activation in response to DNA damage...

..The induction of Egr1 and FOXO3a and its target genes was observed in Jurkat cells transduced by Tat alone. Tat-dependent activation of the Egr1-PTEN-FOXO3a pathway provides a mechanism for HIV-1-associated CD4(+) T cell death...

A protein phosphatase feedback mechanism regulates the basal phosphorylation of Chk2 kinase in the absence of DNA damage

The checkpoint kinase Chk2 is an effector component of the ATM-dependent DNA damage response (DDR) pathway. The activation of Chk2 by genotoxic stress involves its phosphorylation on T68 by ATM and additional auto/transphosphorylations...

Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage

..On the other hand, radiation-induced phosphorylation of the 53BP1 N terminus by the ATM (ataxia-telangiectasia mutated) kinase is not essential for 53BP1 foci formation and takes place independently of ..

..Here, we show that doxorubicin (Dox) treatment induces KAP1 phosphorylation at Ser-824 via an ataxia telangiectasia mutated (ATM)-dependent manner, correlating with the transcriptional de-repression of p21WAF1/CIP1 and ..

Association of single nucleotide polymorphisms in ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with clinical and cellular radiosensitivity

The ATM protein kinase is a primary activator of the cellular response to DNA double-strand breaks (DSBs). In response to DSBs, ATM is activated and phosphorylates key players in various branches of the DNA damage response network...

ATM is activated by default in mitosis, localizes at centrosomes and monitors mitotic spindle integrity

This study sought to establish whether functional analysis of the ATM-p53-p21 pathway adds to the information provided by currently available prognostic factors in patients with chronic lymphocytic leukemia (CLL) requiring frontline ..

A subset of chronic lymphocytic leukemia (CLL) carries mutations in ataxia telangiectasia mutated (ATM). Such ATM mutations may be particularly relevant in the setting of del11q, which invariably results in the deletion of one ATM allele...

..This work suggests that, in addition to its key role in nonhomologous end joining, DNA-PKcs also acts in concert with MRN and ataxia telangiectasia-mutated to regulate resection and thus DNA repair pathway choice. ..

Damage that engenders DNA double-strand breaks (DSBs) activates ataxia telangiectasia mutated (ATM) kinase through its auto- or trans-phosphorylation on Ser1981 and activated ATM is one of the mediators of histone H2AX phosphorylation on ..

The ataxia-telangiectasia-mutated (ATM) kinase plays a central role in responses to various forms of DNA damage and has been suggested to facilitate human immunodeficiency virus type 1 (HIV-1) integration...

The gene that is mutated in ataxia-telangiectasia (A-T), ATM, is catalytically activated in response to DNA damage. Yet a full accounting for the CNS deficits in human A-T or its mouse models remains elusive...

..with a characteristic hypersensitivity to ionizing radiation that is caused by biallelic mutations in A-T mutated (ATM), a gene encoding a protein kinase critical for the induction of cellular responses to DNA damage, particularly to ..

Functional variations in the ATM gene and susceptibility to differentiated thyroid carcinoma

This study addresses the prevalence of ATM mutations and the association with breast cancer in Austrian families selected for a history of breast or ovarian cancer or both [hereditary breast and ovarian cancer (HBOC)]...

A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci

Mutations in the ATM gene are responsible for the autosomal recessive disorder ataxia-telangiectasia (A-T). Many different mutations have been identified using various techniques, with detection efficiencies ranging from 57 to 85%...

..In addition, we also demonstrated that ARK5, when activated by Akt, phosphorylated the ATM protein that is mutated in the human genetic disorder ataxia-telangiectasia and also induced the phosphorylation of ..

..The gene, named ataxia- telangiectasia mutated (ATM) is a recognized component of the response mechanism to DNA double strand breaks...

JASON MARK BECKTA; Fiscal Year: 2014

..Recently, data has arisen demonstrating that the ataxia telangiectasia-mutated (ATM) kinase mediates this checkpoint, conflicting with older reports which posit that ATM has no part in executing cell ..

Peter J McKinnon; Fiscal Year: 2016

..telangiectasia (A-T), which results from loss of function of the DNA damage-signaling serine/threonine kinase ATM (ataxia telangiectasia, mutated), exemplifies the importance of genome stability in the nervous system...

..preeclampsia have focused on mediators of hypertension including autoantibodies to angiotensin II type I receptor (AT1-AA) and anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 despite the observation that many women ..

..that a) circulating and paracrine Ang II is taken up by proximal tubule cells in culture or by the kidney via an AT1 (AT1a) receptor-mediated mechanism;b) microinjection of Ang II directly into the cells can induce intracellular ..

..have evidence that a) circulating and paracrine Ang II is taken up by PT cells in culture or by the kidney via an AT1 (AT1a) receptor-mediated mechanism;b) microinjection of Ang II directly into the cells can induce intracellular ..

..the effects of maternal high salt ingestion on the development of fetal swallowing behavior, ANG receptor subtypes-AT1?R and AT2-R, and vascular homeostasis, as well as long-term programming influence on cardiovascular regulation in ..

..blood pressure, and the physiological mechanisms involved in this effect include angiotensin type 1 receptor (AT1-R)-mediated activation of sympathetic vasomotor neurons at the paraventricular nucleus of the hypothalamus (PVN)...

JoAnn Sekiguchi; Fiscal Year: 2014

..The gene mutated in A-T, ataxia-telangiectasia mutated (ATM), has been identified and encodes a large serine-threonine protein kinase...

..Recent work suggests that brain AngII is involved in the regulation of stress responses. Central AngII and AngII AT1 receptor expression increase during stress and, in turn, activate both the sympathoadrenal and neuroendocrine ..

..These studies are designed to test the overall hypothesis that inhibition of AT1R in the subfornical organ will limit stress responding and alleviate the deleterious consequences of chronic stress exposure. ..

..It is based on new findings of cross-talk between epidermal receptor and the Ang II type 1 (AT1) receptor in extracellular signal-response kinase (ERK), as well as involvement of several non-receptor tyrosine ..

Funds are requested for partial support towards the 14th International Workshop on Ataxia-Telangiectasia and ATM, which will be held at the Crowne Plaza Hotel in Redondo Beach, CA. on April 11-14, 2010...

..This work will focus on the interaction of cdks with DNA damage pathways. Cdks are major targets of ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) checkpoint cascades in response to DNA damage, and ..

..Funds are requested for partial support towards the 15th International Workshop on Ataxia- Telangiectasia and ATM, (ATW2012) which wil be held at the India Habitat Center, Delhi, India (http://www.indiahabitat...

..The goal of this research project is to (1) clarify the functions of Wip1 in the ATM (Ataxia Telangiectasia Mutated) initiated DNA damage response pathway;(2) determine if inhibiting Wip1 would rescue ATM deficiency in ..

..die during the second or early third decade of life and while the genetic lesions responsible for AT (called ATM, for AT-mutated) were first identified in 1988, no known therapy has been identified...

..In addition, it has been estimated that up to 1% of the general population carries mutations in one allele of the ATM (ataxia-telangiectasia mutated) gene and ATM heterozygotes have an increased risk of developing breast cancer...

..subjects who are heterozygotes for mutation in the gene presently identified as a cause of ataxia-telangiectasia (ATM) have a higher that expected risk of cancer, with a primary focus on breast cancer. Specific aims are the following...

Ataxia telangiectasia (A-T) results from mutation of the ATM gene. Individuals with an ATM mutation in one allele are spared from most of the symptoms of the disease, but are more susceptible to cancer and ischemic heart disease...

..the results of radiotherapy we propose to increase the intrinsic radiosensitivity of GBM by selectively targeting ATM (Ataxia-Telangiectasia mutated), which is a key mediator of the DNA damage surveillance pathway in an irradiated ..